(253 days)
RELiZORB™ is indicated for use in pediatric patients (ages 5 years and above) and adult patients to hydrolyze fats in enteral formula.
RELiZORB is a single-use, point-of-care digestive enzyme cartridge that connects in-line with existing enteral feeding circuits. RELiZORB is designed to hydrolyze (digest) fats contained in enteral formulas from triglycerides into fatty acids and monoglycerides to allow for their absorption and utilization by the body. This hydrolysis of fats by RELiZORB is intended to mimic the function of the digestive enzyme lipase in patients who do not excr ete sufficient levels of the lipase enzyme. RELiZORB is comprised of a clear cylindrical, plastic cartridge with a single inlet connection port and a single outlet connection port. Inside the cartridge, there are small white beads. The digestive enzyme, lipase, is covalently bound to the small white beads. The lipase-bead complex, iLipaseTM (immobilized lipase), is retained within the cartridge during use by filters on both ends of the cartridge. The fat in enteral formulas is hydrolyzed as it comes in contact with iLipase as the formula passes through the cartridge.
This document is a 510(k) summary for the RELiZORB™ device, submitted by Alcresta Therapeutics, Inc. The purpose of the submission is to expand the indications for use to include pediatric patients (ages 5 years and above) and to update the shelf life. The device, an enzyme-packed cartridge, is designed to hydrolyze fats in enteral formulas.
Here's an analysis of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a quantitative format for the clinical study. However, it describes the outcomes and findings from the clinical study that supported the expanded indication. For shelf life, it generally states "Shelf life test results support labeled shelf life of RELiZORB," implying that the performance met internal criteria.
| Acceptance Criteria (Inferred from study outcomes) | Reported Device Performance |
|---|---|
| Safety and Tolerability (evaluated through GI symptoms and adverse events) in pediatric and adult patients with CF | The most commonly reported GI events were abdominal pain, gas and bloating, while the most common non-gastrointestinal adverse event reported was headache. The implication is that these were acceptable given the patient population and the overall context of the study. |
| Efficacy in fat absorption (measured by plasma concentrations of LCPUFAs like DHA and EPA) in pediatric and adult patients with CF | RELiZORB use resulted in a 2.8-fold change in plasma concentrations of physiologically relevant long-chain polyunsaturated fatty acids (LCPUFAs) such as DHA and EPA, as measured by plasma absorption kinetics and bioavailability profile (Area Under the Curve - AUC). |
| Additionally, there was a 2.1-fold change in peak plasma concentrations (Cmax) of DHA and EPA. These results confirmed previous findings in a porcine model. | |
| Shelf Life (tensile, mechanical strength, flow rate, hydrolysis, microbiological testing) | "Shelf life test results support labeled shelf life of RELiZORB." (Specific numerical acceptance criteria and performance values are not provided in this summary). |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set (Clinical Study): 33 evaluable patients completed the study (from an initial enrollment of 35 patients; 2 withdrew before exposure).
- Data Provenance: The study was a "multicenter, randomized, double-blind, placebo-controlled crossover clinical study in adult and pediatric patients with cystic fibrosis (CF)." While the specific country of origin is not explicitly stated, "multicenter" implies multiple sites, likely within the United States given the FDA submission. The study design is prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not applicable to this device and study. The RELiZORB device is an enzyme-packed cartridge; its "ground truth" for performance is based on biochemical hydrolysis of fats and physiological absorption, not subjective expert interpretation of images or other data that require inter-rater agreement. The "ground truth" for efficacy was established through objective biochemical markers (LCPUFAs in plasma).
4. Adjudication Method for the Test Set
This is not applicable as the outcome measures (LCPUFA concentrations, adverse events) are objective and do not require adjudication by experts in the way clinical images or diagnoses might.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
This is not applicable. The RELiZORB is a medical device (enzyme-packed cartridge), not an AI-powered diagnostic or assistive technology for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This is not applicable. The RELiZORB is a physical device, not an algorithm. Its performance is inherent to its enzymatic activity.
7. The Type of Ground Truth Used
For the clinical study, the ground truth for device efficacy was established using outcome data:
- Plasma absorption kinetics and bioavailability profile (Area Under the Concentration Time Curve - AUC) of physiologically relevant long-chain polyunsaturated fatty acids (LCPUFAs) like DHA and EPA.
- Peak plasma concentrations (Cmax) of DHA and EPA.
- Gastrointestinal (GI) symptoms and non-GI adverse events for safety and tolerability.
8. The Sample Size for the Training Set
This is not applicable to the RELiZORB device. The device is not learning or being trained in a computational sense. Its design and enzymatic function are pre-defined.
9. How the Ground Truth for the Training Set Was Established
This is not applicable for the same reasons as #8.
§ 876.5985 Enzyme packed cartridge.
(a)
Identification. An enzyme packed cartridge is anex vivo prescription device that is used in enzymatic hydrolysis of macronutrients into their essential nutrient forms at the time of delivery. The device consists of an outer casing containing an inert polymer with a covalently bound enzyme through which nutritional formula is directed. The device fits in line with enteral feeding systems.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The patient contacting components of the device must be demonstrated to be biocompatible.
(2)
In vivo testing must be performed and must demonstrate that the device causes neither an adverse tissue response nor adverse performance.(3) Non-clinical testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be demonstrated:
(i) Mechanical testing to demonstrate that the device can withstand clinical forces;
(ii) Flow rate and leakage testing to demonstrate that the device does not impede the flow of enteral formula;
(iii) Demonstration of enzymatic effect on intended macronutrient;
(iv) The amount of enzyme that exits the cartridge must be characterized;
(v) Validation that the device does not adversely impact the nutritional composition of enteral formula; and
(vi) Validation that the device does not impede flow alarms on enteral feeding pumps.
(4) Human factors testing must be performed to characterize use error risks.
(5) Performance data must support shelf life by demonstrating package integrity and device functionality over the identified shelf life.
(6) Labeling must include the following:
(i) A detailed summary of
in vivo testing pertinent to use of the device, including device-related adverse events;(ii) A detailed summary of compatible formulas that is supported by non-clinical testing, including the expected enzymatic conversion as a percentage;
(iii) Detailed instructions on how to place the device into an enteral feeding circuit;
(iv) A warning regarding the possibility for misconnections; and
(v) Expiration date or shelf life.
(7) Patient labeling must be provided and must include:
(i) Relevant warnings, precautions, adverse effects, and complications;
(ii) A description of the device and how it operates;
(iii) Instructions on how to correctly use the device; and
(iv) The benefits and risks associated with the use of the device.